粗榧类二萜天然产物Mannolide B和C的合成及其相关分子的生源合成研究

本项目拟以西双版纳粗榧植物中分离得到的Mannolide B-C为先导化合物进行合成研究， Mannolide B和C具有新颖的多环系多手性中心的完整二萜骨架，是粗榧类环庚三烯酮二萜化合物的生源合成前体化合物。设计采用催化不对称反电子邻苯醌Diels-Alder反应来构筑目标分子中的两个环系及四个相邻的手性中心（其中两个全碳季碳手性中心），再采用羧基诱导的碳氢官能化完成五元内酯环的合成，进而完成Mannolide B和C的全合成；设计采用羧基诱导的碳氢官能化在Mannolide C骨架中心引入三级手性羟基，经仿生转化完成Mannolide A的合成，设计以脱羧和脱氢为关键反应完成Mannolide B到(+)-Harringtonolide的仿生合成转化。此研究对相关粗榧类二萜天然产物的设计与合成及生源合成途径研究具有重要意义。

In this project, the Mannolide B and C, which were isolated from Cephalotaxus mannii Hook f., were studied on synthesis as the lead compounds. These two products possess a new intact C20 diterpenoid skeleton with complex, noble multi-ring system and several stereocentres. This new skeleton could serve as the biosynthetic precursor of Cephalotaxus cephalotane diterpenoids. The designed synthetic strategy utilizes an asymmetric inverse electron-need Diels-Alders reaction of o-quinone as key step to forge two ring systems and four adjacent chiral centres which contain two all-carbon quaternary sterecenters, followed by utilizing C-H functionalization of carboxylic-induced esterification to disclose the total synthesis of Mannolide B and C. After disclosing of Mannolide C, we plan to attach a tertiary chiral hydroxyl group to the middle moiety of Mannolide C skeleton via a key carboxylic-induced C-H functionalization to transfer this product to Mannolide A in a biomimetic manner. And (+)-Harringtonolide can be biosynthesized from Mannolide B through a decarboxylation and dehydration sequence. It is of great significance for these researches on the cephalotaxus diterpenoid natural products of design and synthesis and the biosynthesis pathway.